A new study led by Stanford Medicine scientists demonstrates a simple way of studying organ aging by analyzing distinct proteins, or sets of them, in blood, enabling the prediction of individuals’ risk for diseases.
一項由美國史丹佛大學醫學院，科學家們領導的新研究證實了一種，藉由分析血液中，不同蛋白質或蛋白質組，來研究器官老化的簡單方法，使之能預測個體患病的風險。
圖1. Tony Wyss-Coray宣稱：「我們能估算，於外表上健康人中，器官的生物年齡。」
“We can estimate the biological age of an organ in an apparently healthy person,”Tony Wyss-Coray said.
Like any typical car or house or society, the pace at which parts of our bodies fall apart varies from part to part.
就像任何典型的汽車或房屋、社會一樣，咱們身體各器官崩潰的速度，因器官而異。
A study of 5,678 people, led by Stanford Medicine investigators, has shown that our organs age at different rates — and when an organ’s age is especially advanced in comparison with its counterpart in other people of the same age, the person carrying it is at heightened risk both for diseases associated with that organ and for dying.
一項由史丹佛大學醫學院之調查研究人員們所領導，針對5,678人的研究已經證實，咱們器官以不同的速度老化。當一個器官的老化，相較於其他同年齡者的對應器官特別提早時，具有上述器官的人，冒有升高之與該器官相關疾病及死亡的風險。
According to the study, about 1 in every 5 reasonably healthy adults 50 or older is walking around with at least one organ aging at a strongly accelerated rate.
根據該項研究，在每5名50歲或以上、相當健康的成年人中，大約有1名至少有一種器官正經歷著，以一種強勁加速了的速度老化。
The silver lining: It may be possible that a simple blood test can tell which, if any, organs in a person’s body are aging rapidly, guiding therapeutic interventions well before clinical symptoms manifest.
一線希望：簡單的血液檢查，或許可能判斷，一個人體內的器官(倘若有的話)正迅速老化中，而在臨床症狀出現之前，適切地引領治療的干預。
“We can estimate the biological age of an organ in an apparently healthy person,” said he study’s senior author, Tony Wyss-Coray, PhD, a professor of neurology and the D. H. Chen Professor II. “That, in turn, predicts a person’s risk for disease related to that organ.”
該項研究資深撰文人，史丹佛大學醫學院神經病學及神經科學傑出的D.H. Chen教授，Tony Wyss-Coray博士宣稱：「我們能估算，於外表上健康人中，器官的生物年齡。依序，那能預測一個人，與那器官有關之疾病的風險。」
Hamilton Oh and Jarod Rutledge, graduate students in Wyss-Coray’s lab, are lead authors of the study, which was published online Dec. 6 in Nature.
於Wyss-Coray實驗室的研究生，Hamilton Oh及Jarod Rutledge是該，(2023年)12月6日，發表於線上版《自然》期刊之研究的主要撰文人。
“Numerous studies have come up with single numbers representing individuals’ biological age — the age implied by a sophisticated array of biomarkers — as opposed to their chronical age, the actual numbers of years that have passed since their birth,” said Wyss-Coray, who is also the director of the Phil and Penny Knight Initiative for Brain Resilience.
也是史丹佛大學菲爾暨潘妮奈特大腦復原力倡議的主任，Wyss-Coray宣稱：「諸多研究已經提出，代表個人生物年齡(一系列複雜生物標記所暗示之年齡)的單式年數，而不是打從他們出生以來，已經過的實際年數。」。
The new study went a step further, coming up with distinct numbers for each of 11 key organs, organ systems or tissues: heart, fat, lung, immune system, kidney, liver, muscle, pancreas, brain, vasculature and intestine.
該項新研究更進一步提出了，有關心臟、脂肪、肺、免疫系統、腎臟、肝臟、肌肉、胰臟、大腦、脈管系統及腸道等，11種關鍵器官、器官系統或組織，每一種不同的年數。
“When we compared each of these organs’ biological age for each individual with its counterparts among a large group of people without obvious severe diseases, we found that18.4% of those age 50 or older had at least one organ aging significantly more rapidly than the average,” Wyss-Coray said. “And we found that these individuals are at heightened risk for disease in that particular organ in the next 15 years.”
Wyss-Coray宣稱：「當我們將每個人之此些器官的每一生物年齡，與一大群沒有明顯嚴重疾病者的對應器官進行比較時，我們發現，那些50歲或以上者中，18.4%至少有一個器官老化速度，明顯更快速於平均數。且我們發現，此些人在那特定器官方面，於未來15年內，冒有升高的疾病風險。」
Only about 1 in 60 people in the study had two organs undergoing aging at that fast clip. But, Wyss-Coray said, “They had 6.5 times the mortality risk of somebody without any pronouncedly aged organ.”
在該項研究中，僅約六十分之一的人，有兩個器官以那快的速度經歷老化。 不過，Wyss-Coray宣稱「他們有6.5倍於，沒有任何明顯老化器官者的死亡風險。」
Using commercially available technologies and an algorithm of their own design, the researchers assessed the levels of thousands of proteins in people’s blood, determined that nearly 1,000 of those proteins originated within one or another single organ, and tied aberrant levels of those proteins to corresponding organs’ accelerated aging and susceptibility to disease and mortality.
使用商業上可資取得的技術及他們自己設計的演算法，此些研究人員評估了，人們血液中，數千種蛋白質的水平。確認了，那些中近1千種蛋白質，起源於一個或另一個單一器官，並將此些蛋白質的異常水平，與對應器官的加速老化，及對疾病與死亡的易受影響性聯繫起來。
They started by checking the levels of nearly 5,000 proteins in the blood of just under 1,400 healthy people ages 20 to 90 but mostly in mid- to late stages of life, and flagging all proteins whose genes were four times more highly activated in one organ compared with any other organ. They found nearly 900 such organ-specific proteins, which they whittled down to 858 for purposes of reliability.
他們首先檢查了，近1,400名年齡20至90歲，不過大多數處於生命中到後期之健康人血液中，近5千種蛋白質的水平。並標記了於一個器官中，其基因相較於任何其他器官，更高度被活化四倍的所有蛋白質。他們發現了，近900種此類器官特異性的蛋白質。為了可靠性的目的，他們將其削減到858種。
To do this, they trained a machine-learning algorithm to guess people’s age based on the levels of those nearly 5,000 proteins. The algorithm tries to pick proteins that best correlate with a trait of interest (in this case, accelerated biological aging in a person or in a particular organ) by asking, one by one, “Does this protein enhance the correlation?”
為此，他們訓練了一種機器學習演算法，根據那些近5千種蛋白質的水平，來猜測人們的年齡。該演算法試圖藉由逐一探究，來挑選出具有感興趣之特質(在此實例中，加速了於一個人或一個特定器官中的生物老化)最相關的蛋白質。「這種蛋白質，提升了相互關係？」
The scientists verified the algorithm’s accuracy by assessing the ages of another 4,000 or so people who were somewhat representative of the U.S. population.
Then they used the proteins they’d identified to zero in on each of the 11 organs they’d selected for analysis, measuring levels of organ-specific proteins within each individual’s blood.
此些科學家們藉由評估，在某種程度上代表了，美國人口之另外4千人左右的年齡，來驗證該演算法的準確性。之後，使用了他們已經確認的此些蛋白質，來將目標集中於，他們已經選擇供分析之上述11種中的每一器官，測量每一器官血液中之特異性蛋白質的水平。
While there was some modest aging synchrony among separate organs within any person’s body, that person’s individual organs largely went their separate ways along the aging path.
儘管於任何人體內的不同器官之間，多少有些適度的衰老同步性，不過人的各個器官大部分順著老化途徑，進行其各自的進程。
For each of the 11 organs, Wyss-Coray’s team came up with an “age gap”: the difference between an organ’s actual age and its estimated age based on the algorithm’s organ-specific-protein-driven calculations.
對上述11種器官中的每一種，Wyss-Coray的團隊皆提出了一個“年齡差異”：也就是，器官的實際年齡，與其根據該演算法之器官特異性蛋白質驅動的計算，所估測之年齡間的差異。
The researchers found that the identified age gaps for 10 of the 11 organs studied (the only exception being intestine) were significantly associated with future risk of death from all causes over 15 years of follow-up.
此些研究人員發現，這11種經研究確認了年齡差異的器官中，有10種(唯一的例外是腸道)顯著與，在後續探究的15年間，源自各種原因之死亡的未來風險有所關聯。
Having an accelerated-aging organ (defined as having a 1-standard-deviation higher algorithm-scored biological age of the organ than the group average for that organ among people of the same chronological age) carried a 15% to 50% higher mortality risk over the next 15 years, depending on which organ was affected.
擁有加速了老化的器官(被定義為，具有該器官比在同齡人群中，那器官的群體平均年齡，更高1個標準差之演算法評分的生物學年齡)，在往後15年間，具有高出15%至50%的死亡風險。這取決於，哪種器官受到影響。
People with accelerated heart aging but initially exhibiting no active disease or clinically abnormal biomarkers were at 2.5 times as high a risk of heart failure as people with normally aging hearts, the study showed.
該項研究顯示，具有加速了心臟老化，不過最初沒有展現出，進展中的疾病，或臨床上異常之生物標記者，心臟衰竭的風險，是具有心臟正常老化者的2.5倍。
Those with“older” brains were 1.8 times as likely to show cognitive decline over five years as those with “young” brains. Accelerated brain or vasculature aging — either one —predicted risk for Alzheimer’s disease progression as well as the best currently used clinical biomarkers do.
那些具有“較高年歲”大腦者，在五年間出現認知能力下降的可能性，是具有“較低年歲”大腦者的1.8倍。加速了大腦或脈管系統老化(任一種)，與目前最被使用之臨床生物標記一樣，預測了阿茲海默症進展的風險。
There were likewise strong associations between an extreme-aging (more than 2 standard deviations above the norm) kidney score and both hypertension and diabetes, as well as between an extreme-aging heart score and both atrial fibrillation and heart attack.
同樣地，除了在極度老化的心臟評分與心房顫動及心臟病發作兩者間之外，在極度老化(超出正常值，多於2個標準離差)的腎臟評分，與高血壓及糖尿病兩者間，也有極大的關聯性。
“If we can reproduce this finding in 50,000 or 100,000 individuals,” Wyss-Coray said, “it will mean that by monitoring the health of individual organs in apparently healthy people, we might be able to find organs that are undergoing accelerated aging in people’s bodies, and we might be able to treat people before they get sick.”
Wyss-Coray宣稱：「倘若我們能在5萬或10萬人中，重現此發現。這將意味著，藉由監測於外表上健康者，各個器官的健康狀況，我們或許能發現，於人們體內正經歷加速了老化的器官，從而我們或許能在人們生病之前，進行處置。」
Identifying the organ-specific proteins that best indicate excessive organ aging and, consequently, elevated disease risk could also lead to new drug targets, he said.
他表示，確認最佳顯示過度器官老化，及從而升高了疾病風險之器官特異性的蛋白質，也可能引領出新的藥物標的。
Wyss-Coray, Oh and Rutledge have co-founded a company, Teal Omics Inc., to explore the commercialization of their findings. Stanford University’s Office of Technology Licensing has filed a patent application related to this work.
Wyss-Coray、Oh及Rutledge業已共同創立了一家，探索其研究發現商業化的公司─Teal Omics Inc.。史丹佛大學技術許可辦公室，已徑提出一項與該研究相關的專利申請。
網址：https://med.stanford.edu/news/all-news/2023/12/aging-organs.html
翻譯：許東榮
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